788 Medicina (Kaunas) 2006; 42(10)

Exercise as a stressor to the human neuroendocrine system

Anthony C. Hackney
Endocrine Section, Applied Physiology Laboratory, Department of Exercise and Sport Science,
Department of Nutrition, School of Public Health and Medicine,
University of North Carolina, Chapel Hill, North Carolina, USA

Key words: hormones; physical activity; stress.

Summary. This article is a brief review on the effects of exercise stress upon the major hormonal
components that make up the human neuroendocrine system. The review is organized into four
major topics, which are presented and dealt with in the form of questions. These questions are:
1) Is exercise a stressor to the neuroendocrine system? 2) Why would exercise be a stressor to the
neuroendocrine system? 3) What are the effects of exercise as a stressor upon the neuroendocrine
system? 4) Is exercise always a stressor to the neuroendocrine system? These questions are
addressed and answered in the article in an attempt to provide fundamental background knowledge
on neuroendocrine response to exercise.

Introduction reader and then answered in the course of the article.

Men and women who currently compete in spor-
ting events are swimming, running, cycling, and ska-
ting faster than ever before. This is attested to by the
fact that world records in many sporting events are
being broken on nearly an annual basis. The factors
that contribute to this improvement in human perfor-
mance are many, but perhaps the most important, is
the greater level of exercise training that athletes are
performing in our modern era. This enhanced volume
of exercise training results in an extreme amount of
stress being placed on the human organism. Such stress
induces many physiological changes and adaptations
that are highly beneficial to the sporting persons and
their ability to perform exercise (1). In humans, one
physiological system that is extremely responsive to
the stress of exercise and exercise training is the neu-
roendocrine system (2–4).
The purpose of this article is to present a concise
synopsis of the effects of exercise (i.e., physical acti-
vity) upon the major hormonal components that help
comprise the human neuroendocrine system. The
intent here is for this article to serve as a “primer” for
those persons who may have a limited background in
the area of “exercise physiology” and in particular
the neuroendocrine responses to exercise. The discus-
sion is meant as an introduction to the topic, and thus
the level of depth is delimited to just major aspects
and key points. The review is organized into four ma-
jor topics, and these topics are presented in a didactic
approach using questions which are proposed to the
Correspondence to Professor Dr. A. C. Hackney, Applied Physiology Laboratory, University of North Carolina,
CB # 8700 Fetzer Building, Chapel Hill, NC 27599-8700, USA. E-mail: ach@email.unc.edu
Question 1 – Is exercise a stressor
to the neuroendocrine system?
In the title to this article, it is implied that exercise
is stressful to human beings. Nonetheless, the first
question (noted above) is proposed in order to address
whether this is a valid assumption. To answer this
question, it is perhaps best to begin by providing a
definition of what is “stress.” The Merriam-Webster’s
English Dictionary supplies 11 different definition of
the word “stress” (5). What appears to be the most
appropriate to this article and in the physiological
context is the following:
“Stress is a specific response by the body to a sti-
mulus that disturbs or interferes with the ‘normal’
physiological equilibrium of an organism.”
A key word in this definition is “normal,” and it is
important in the context of this article to recognize
that stress responses would be considered those
beyond the typical, daily (i.e., natural) basal physio-
logical responses and events, but not events that would
be considered “distressful” in nature (e.g., to observe
a murder occurring). Furthermore, the above definition
can be enhanced and expanded upon by the answering
of the logical follow-on question, “What is a stressor?”
The Merriam-Webster’s Dictionary provides this de-
finition:
“Stressor is an activity, event, or stimulus that cau-
ses stress.”
A brief search of the research literature would
 Exercise as a stressor to the human neuroendocrine system 789

reveal that there are thousands of published research Table 1. The following are abbreviations used
studies which have shown the “normal” neuroendoc- throughout this article as well as ones typically
rine, resting equilibrium (i.e., homeostasis) is distur- found in the area of endocrinology
bed by a bout of exercise (i.e., a executed period of
physical activity in which the metabolic rate is signi- Name Abbreviations
ficantly elevated above rest for a period of time) (6). Adrenocorticotropic hormone ACTH
These research findings, when compared to the defi- Atrial natriuretic peptide ANP
nition above, would support the answer that, “yes,” Arginine vasopressin AVP
exercise is a “stressor” to the neuroendocrine system b-Endorphin b-END
(nota bene, the most applicable type of exercise that Central nervous system CNS
the findings in this article applies to are dynamic, large Corticotropin releasing hormone CRH
muscle groups, so-called aerobic activities; e.g., run- Decrease ¯
ning and walking). Delta (i.e., change) D
Follicle-stimulating hormone FSH
Question 2 – Why would exercise be a stressor Growth hormone GH
to the neuroendocrine system? Growth hormone releasing hormone GHRH
To answer to this question, one must first come Increase -
back to what is the basic physiological role of the neu- Insulin-like growth factor-1 IGF1
roendocrine system (NES; Table 1 contains a list of Luteinizing hormone LH
abbreviations used throughout this article). In the Metabolic clearance rate MCR
classic definition, the NES is referred to as a series of Neuroendocrine NE
ductless glands (and neurons) that release chemical Neuroendocrine system NES
messengers called “hormones” into the circulatory Peripheral nervous system PNS
system. These hormones in turn act to aid in the control Prolactin PRL
and regulation of various physiological processes and Sympathetic nervous system SNS
organ system functions, such as metabolism, the car- Thyrotropin-releasing hormone TRH
diovascular-respiratory system, hydration status, ther- Thyroid-stimulating hormone TSH
moregulation, digestion, growth-maturation, and rep- Thyroxine T4
roduction (7, 8). Triiodothyronine T3
Evidently, many of these physiological processes
and organ systems just noted are essential to the body’s
ability to perform exercise. Put another way, changes “chronic” form where one is dealing with the effects
in many of these bodily processes are necessary in of a exercise training program (e.g., several weeks of
order to bring about the physiologic accommodation near daily exercise bouts, which have an accumulative
required to meet the demands of exercise (2). The NES physiological adaptation effect). These distinctions in
is a primary regulator and modifier of many of these terminology are important since the definition and
accommodations (9). Thus, as organisms we need the categorization of responses of the NES to exercise
NES to respond to the stress of exercise in order to can vary greatly depending upon which form of exer-
allow the human body to be able to accommodate phy- cise you are focusing upon. Table 2 presents a sum-
siologically and perform exercise. mary and explanation of some of the common termi-
nologies used to describe exercise forms and types.
Question 3 – What are the effects of exercise Secondly, it is important to understand how resear-
as a stressor upon the neuroendocrine system? chers go about quantifying and assessing the “response
It is necessary, before answering this question, to of the NES” to exercise. The most typical and accepted
address several points in order to appreciate fully the way for clinicians and researchers to do this assess-
complexity of the answer. First, the word “exercise” ment is to measure circulating hormonal concentra-
does not have a universal meaning for all researchers, tions in the blood (or perhaps saliva and/or urine spe-
nor is it translated uniformly in the research literature. cimens) from the endocrine gland of interest. The
For example, exercise can be thought of in its “acute” findings noted in this article are principally based upon
form when one is speaking about a single bout of exer- such assessment. However, the blood assessment
cise (e.g., 30 minutes of brisk walking at a significantly technique has limitations in its ability to tell resear-
elevated heart rate), or it can be thought of in its more chers what is exactly going on within a very dynamic

Medicina (Kaunas) 2006; 42(10)

790 Anthony C. Hackney

Table 2. A categorization and definition of exercise intensity and exercise-type relative to exercise
studies of physically fit individuals. In quantifying exercise intensity, it is typical to express it as a
relative percentage of an individual’s maximal oxygen uptake (VO2max; i.e., maximal aerobic capacity)

Relative intensity Energy pathway Typical Other

Category term
(%VO2max) predominating duration terminology
Light or easy exercise <35% Aerobic >30 min Short-term, submaximal
Moderate exercise 35–70% Aerobic 30–180 min Submaximal prolonged
Aerobic – <120 min Submaximal prolonged,
Heavy exercise >70%
Anaerobic high intensity
Aerobic – <15 min Maximal or max, high
Maximal exercise 100%
Anaerobic intensity
Supramaximal
>100% Anaerobic <1 min Sprints, power
exercise

Based upon work by C. Bouchard et al. in Exercise, Fitness, and Health: A Consensus of Current Knowledge
(Champaign, IL. Human Kinetics, 1990) as reported by A. C. Hackney and J. Dobridge (reference 20).

system. For instance, changes in circulating hormonal
concentrations are brought about not only by changes
in glandular production and secretion, but also by
changes in the metabolic clearance rate (MCR) for
the hormone (8). During an exercise bout MCR can
vary either through changes in target tissue uptake or
hormonal degradation. Additionally, for some hormo-
nes the binding affinities of carrier protein change
during exercise thereby making more or less of the
hormonal free form available in the circulation (10).
Thus, by measuring just blood hormonal concentration
values, it is sometimes difficult to determine what me-
chanism is causing the NES response observed. Fur-
thermore, in some situations the hormonal response
observed is being influenced by hemoconcentration
or hemodilution events associated with plasma fluids
shifting in and out of the vascular bed during exercise
(11). Consequently, when assessing the NES responses
to exercise by examining circulating hormonal con-
centrations, it is important to try to take into account
such factors as just mentioned above, if there is an
attempt to discern “what” is really happening and
“why” it is happening physiologically. To try and over
come of these limitations, some endocrinologists uti-
lize area-under-the-curve analysis to get a more “dy-
namic” picture of hormonal events and endocrine
function. This process involves taking multiple blood
samples (or saliva in some cases) over a several hour
period and then plotting the concentration responses
and integrating the response curve, and the integrated
response is evaluated (12). This technique has promise
for providing some degree of further information; ho-
wever, it is still influenced by some of the same factors
noted above and can be considered more invasive due
to the multiple specimen collection. Another technique
of assessment involves a pharmaceutical challenge to
an endocrine gland. That is, a drug or compound that
stimulates hormonal release is infused into an
individual, and then multiple blood (or saliva) samples
are collected afterwards to evaluate the endocrine
glands responsive by looking at hormonal changes.
This technique provides excellent information on the
responsiveness (e.g., production and secretions rates)
and can serve as a good clinical tool but can have
higher health risks and invasive aspects as well as also
being influenced by some of the above factors.
Next, in order to answer the third question posed
in the title to this section, initially it is convenient to
address the NES responses to “acute exercise” (i.e., a
single bout) and later in the article to discuss “chronic
exercise” (i.e., exercise training). In a single, acute
exercise bout, there are several components that dic-
tate what will be the magnitude and direction of the
NES response. The key components of “acute exer-
cise” are the intensity at which the exercise is per-
formed and the duration of the individual exercise
bout (1, 13, 14).
Typically the greater the intensity of exercise, the
greater the degree of stress placed upon the NES and
the more exacerbated the hormonal response becomes,
meaning there are greater disturbances in the circu-
lating hormonal concentrations (1, 13, 15). The exact
nature (i.e., direction) of the responses one might see
in the circulating hormonal concentrations is varied.
Fig. 1 displays a generalized representation of such
hormonal responses with an exercise bout of progres-

Medicina (Kaunas) 2006; 42(10)

 Exercise as a stressor to the human neuroendocrine system 791

sively increasing intensity. As can be seen in the figure,
hormonal response can take several forms. It could
be linear or curve linear in nature or involve a thres-
hold intensity needing to be reached before any res-
ponse is observed (12). In addition, the response is
not always necessarily increased circulating amounts
of hormone, as some hormones can decrease in their
levels in response to acute exercise (see Fig. 1).
Relative to duration, typically extending the length
of time of an exercise bout at any given intensity tends
to amplify an NES response; that is, as a person exer-
cises longer and longer, one can see a gradual and
further increase (or decrease; depending upon the
specific hormone being examined) in the circulating
hormonal levels (15). Furthermore, in some situations
after the initial change in the hormonal concentration,
there can be a plateau (i.e., steady state) of the response
even as exercise duration continues.
In addition to the intensity-duration components
that can influence the NES response to an acute
exercise bout, there are several other factors that can
modify the response such as mode of activity, envi-
Hormonal response
ronmental conditions, age, gender, nutrition, circadian
rhythms, genetics, and exercise training status. Each
of these factors is briefly addressed below.
Some excellent research work by the North Ame-
rican investigator, William Kraemer, and his associa-
tes over the years has helped researchers to recognize
that the hormonal responses to various forms of
resistance exercise can differ from that of an aerobic
exercise sessions, such as running or bicycling for
examples (16–18). While there is limited research in
exercise endocrinology dealing with swimming, some
evidence suggests it may produce some differing NES
responses in some respects to other modalities of
activities (2, 3, 19). This mode of activity differences
can be due to a variety of features associated with the
aerobic and anaerobic nature of the activities, such as
muscle fiber recruitment patterns, activation of energy
production pathways, and utilization of different subs-
trates, postural differences, and hemodynamic dispa-
rities. For more explanation and details on these mode
phenomena, the reader is directed to select research
references (see 12, 17, 20).

Rest 20 30 40 50 60 70 80 90 100
Exercise intensity (%VO2)

Fig. 1. Differences in the type of hormonal responses to an exercise bout of increasing intensity
The Y-axis is an arbitrary scaling used only to indicate direction of hormonal changes. The X-axis
represents exercise intensity in percentage of maximal oxygen uptake (%VO2).

Medicina (Kaunas) 2006; 42(10)

792 Anthony C. Hackney
The ambient environmental condition, a person is
exposed to, can have great influences on the NES.
For example, the more ambient temperatures deviate
from what is typically normal for a person, or their
heat storage status is some how altered, or they ex-
perience hypoxemia upon going to altitude, the more
the hormonal response to exercise can become dis-
torted from normal (21, 22). In some situations, en-
vironmental factors can dramatically amplify certain
hormonal responses; in other situations, the ambient
environment may provoke hormonal changes that are
usually not seen with an exercise bout of a respective
intensity or duration (9).
Age and maturation can also be influential factors.
The very young and older mature individuals have
certain NES responses to exercise that vary (e.g.,
typically lessened) from those exhibited by the young
to middle-aged adults (i.e., college-aged) which
usually are used in many exercise studies (12). These
differing responses may represent an incomplete
developmental process of the NES in children or
apoptotic processes occurring in certain endocrine tis-
sue of the elderly (23, 24).
The issue of gender differences in NES responses
typically revolves around the influence of the mens-
trual cycle and the reproductive hormones in women
upon other hormones and how that may in turn modify
their NES response to exercise (25). However, certain
nonreproductive hormones can also be vastly different
between males and females too, for example the adi-
pocyte hormone leptin. Regrettably, too few resear-
chers seem to be mindful of such gender differences
in hormonal concentrations when studying exercise
physiology. For more information on this topic, the
reader is directed to references 1, 12, and 25.
Nutrition status and dietary intakes that deviate
greatly from normal have been shown to influence
the NES responses to exercise, causing some hormonal
responses to be augmented and others to be attenuated
(2, 19).
Many hormones exhibit circadian rhythms and
diurnal variations in their circulating concentrations.
Work by several research groups has shown that the
relative magnitude of the NES response to exercise
for some hormones is variable based upon the time of
day in which the exercise takes place – this is even
when accounting for differences in resting-basal con-
centrations, circadian pattern effects of the different
times of day, and standardizing the exercise amount
(25–27). Thus, exercise of the same duration and in-
tensity performed at two different times of the day
could provoke several magnitudes of difference in hor-
monal response. Interestingly, some hormones show
a greater response to exercise in the morning than af-
ternoon, and the responses of some hormones are op-
posite; however, this chronobiology issue has not been
studied fully, and additional work is necessary before
a complete summarization of hormone, exercise res-
ponse, and time-of-day effects can be summarized
adequately.
There is also genetic variation among people and
this can result in some degree of NES responses that
are different than expected. Atko Viru of Estonia has
been a proponent of this factor influencing research
outcomes in exercise endocrinology for many years
(22, 24). Researchers may need to examine this factor
much more closely in the future to better understand
the hormonal response to the stress of exercise.
Lastly, it is important to recognize that exercise
training itself can modify the subsequent exercise
response to an acute exercise bout after training adap-
tations have occurred. In most cases, the NES respon-
ses to exercise become attenuated to some degree by
prolonged exposure to appropriate levels of exercise
training (as noted earlier, this point will be addressed
later in the article) (2, 28).
This has been a long preamble to get to the answer
for the third question, “What are the effects of exercise
as a stressor upon the neuroendocrine system?” The
discussion thus far should make the reader aware that
multiple factors could be put together in different com-
binations to answer that specific question concisely.
Therefore, for the sake of conciseness, only a single
exercise example (i.e., bout) will be discussed and
explained in detail to illustrate the point of what can
happen. This example involves looking at an exercise
bout involving a dynamic, large muscle group, aerobic
activity (e.g., running) for roughly 30- to 45-minute
duration, at a moderately hard intensity corresponding
approximately to 70% of an individual’s maximal
oxygen uptake (this intensity would correspond to
about 80% of an individual’s heart rate maximum).
In addition, for organizational purposes, a concept
from Henrik Galbo is used to divide the NES responses
into phases (2, 3). The first phase is immediately at
the onset of exercise, taking just seconds to occur. It
consists primarily of increased sympathetic nervous
system (SNS) activation with the onset of body mo-
tion. The increased SNS activity could also be a result
of anticipation to the stress of the ensuing exercise.
This increased SNS activity results in catecholamine
release at target tissues directly, as well as elevations
Medicina (Kaunas) 2006; 42(10)
 Exercise as a stressor to the human neuroendocrine system
in circulating catecholamine from so-called sympa-
thetic “spill-over” effects. This effect is further ampli-
fied by the sympathetic connection to the adrenal me-
dullary gland which in turn adds to the circulating
catecholamine response (29). Concurrent with these
sympathetic-adrenal actions, pancreatic insulin secre-
tion begins to be inhibited while glucagon secretion
becomes stimulated (Fig. 2, phase 1). The entire pro-
cess to this point seems to involve feed-forward me-
chanisms of the central nervous system to drive these
initial responses; although, the events are also modi-
fied by peripheral afferent neural input from sensory
receptors of skeletal muscle (29, 30).
Next would be the intermediate or secondary phase
which takes longer to develop, but is still typically
very fast beginning usually in much less than a minute.
In this stage, the hypothalamus begins the process of
releasing its hormones such as CRH, GHRH, and TRH
(see Table 1 for abbreviation definitions) in an attempt
to provoke changes at the pituitary so this endocrine
gland will in turn be stimulated to release its hormones
(see Fig. 2, phase 2). As the pituitary begins to re-
spond to the hypothalamic stimulus, its “trophic hor-
mones” begin to be added to the circulation, and these
hormones begin to act upon their specific peripheral
target glands to stimulate additional hormonal release
(7, 8). One of the fastest acting in this cascade of events
is the hypothalamic-pituitary-adrenocortical interac-
tion where CRH brings about ACTH release and that
in turn brings about cortisol release (Fig. 2, phase 2).
When several endocrine glands are linked together in
such an interacting regulatory capacity, they are typi-
cally referred to as an “axis.” The above example is
thus referred to as the “hypothalamic-pituitary-adreno-
cortical axis” (8, 31).
As exercise continues, there is a transition beyond
the intermediate phase into a third phase of response
which is a more prolonged state. In the phase 3 panel
of Fig. 2, the responses of the sympathetic-adrenal
axis are being augmented by other hormones from
the anterior-posterior pituitary and the peripheral
endocrine glands subordinated to pituitary regulation
(2, 3, 8). Additionally, during this phase the skeletal
and cardiac muscles themselves begin to release their
select cytokines, hormonal-like agents, into the circu-
lation (9, 32, 33).
Neural factors have been the primary stimuli regu-
lating the NES response up to this point. However,
now in the third phase, there is an ever-increasing in-
fluence of the humoral and hormonal factors that regu-
late the overall responses due to the changes in the
Medicina (Kaunas) 2006; 42(10)
793
“internal milieu.” This shifting of primary regulators
allows an increasing reliance upon feedback rather
than feed-forward control mechanism. The influence
of humoral and hormonal stimuli-types in modulating
the hormonal levels is magnified as the exercise
duration is extended, and energy substrate availability
causes shifts in fuel usage (i.e., ¯ carbohydrate Þ -
lipid), or hydration issues (i.e., hemoconcentration
and/or dehydration) begin compromising the thermo-
regulatory ability and heat storage (34, 35). By the
completion of this example exercise bout, many of
the hormones depicted in Fig. 2 would easily display
between a 2- to 10-fold change in their circulating
concentrations from those levels observed at rest
before exercise.
As the exercise ends, we come to the fourth and
last phase – recovery. In recovery, the NES attempts
to return to a normal resting homeostasis, as are the
other physiological systems of the body. The duration
of the recovery period is totally dependent upon the
severity of the exercise bout; that is, how much stress
the NES has been subjected too (36, 37). Opinions
exist that this phase actually deserves to be split into
two distinct phases. That is, research from several
investigators indicates that there is most certainly an
early recovery that occurs within the first few minutes
to hours after exercise, followed by a late recovery
phase lasting many hours in length for certain hor-
mones after exercise ends (26, 38)
The illustrative example just worked through is
by no means complete and exhaustive, as already
mentioned, the exact and specific NES responses
would depend upon how the major components ma-
king up the exercise bout are manipulated (i.e.,
intensity and duration). To provide a more complete
summary of exercise NES events the reader is directed
to Table 3. This table is modified from a book chapter
reviewing exercise endocrinology developed by the
article author and a colleague (12). The table indicates
the direction of hormonal change and the approximate
magnitude of hormonal change for different exercise
activities at a variety of intensities.
Question 4 – Is exercise always a stressor to
the neuroendocrine system?
This question is dealing with the topic of exercise
training or “chronic exercise.” A review of the lite-
rature supports the idea that the answer to this question
is most certainly, “yes” – exercise is always a stress
to the NES. However, it appears that exercise can
become less of a stressor over time as one is repeti-
tively exposed to exercise. As mentioned earlier, the
794 Anthony C. Hackney

CNS
Phase 1

Pancreas
Pituitary SNS

INSULIN (-)
GLUCAGON (+)
Adrenal
Medulla
(NE>E)

PNS
Afferents CATECHOLAMINES
cle
Afferents
Vessel
M us
(E>NE) al
let
S ke

A
-
- Muscular Motion
31

CNS
Phase 2
CRH
GHRH
TRH
Pituitary

ACTH
Adrenal
Cortex
Adrenal
Medull a

PNS
Afferents CORTISOL
c le
Affe rents
Vessel
us
lM
el e ta
Sk

-- Muscu lar Motio n

B

CNS
Humoral Δ Phase 3
CRH p H, ToC, AA, glucose …
PRL bb-END
GHRH Thyroid
ThyroidGland
Gland
TRH
GH TSH
Pituitary

ACTH
Adrenal Free T4, T 3
Cortex IGF1
AVP Adrenal
Medulla

PNS
Afferents
Affe rent s CORTISOL
Vessel le
sc
l Mu
ANP
el eta
Sk
Cytokines

rt
Hea
-
- Muscu lar Mot io n
C33

Fig. 2. Regulation of hormonal secretion by SNS, pituitary gland (and subordinate glands),
and muscle tissues at: (A) onset phase 1, (B) intermediate phase 2, and (C) prolonged phase 3
This example is for an exercise bout of moderate intensity and duration (reference 12).

Medicina (Kaunas) 2006; 42(10)

 Exercise as a stressor to the human neuroendocrine system 795

Table 3. Magnitude and direction of responses of select hormones to exercise bouts

of different mode-type and duration (reference 12)

Exercise type – situation

Hormone anticipation short-term high prolonged resistance aerobic
submaximal intensity exercise exercise training
ACTH + + ++ ++ ++ –
Aldosterone 0 + ++ ++ + 0
AVP 0 + ++ ++ ? 0
Catecholamine + + ++ ++ ++ –
Cortisol + + ++ ++ ++ –
b-Endorphin 0 + or 0 ++ ++ + 0
Estrogens 0 + + ? ? – or 0
FSH 0 + + or 0 +, 0, – ++ –
Glucagon 0 + + ++ ? –
Growth hormone 0 + ++ ++ ++ +
Insulin 0 – – – – –
Leptin 0 + or 0 + or 0 + or 0 + or 0 – or 0
LH 0 + +, 0, – + or – ++ –
Progesterone 0 + + ? ? – or 0
Prolactin + or 0 + ++ + + – or +
T 3, T 4 0 0 0 + or – 0 – or 0
Testosterone 0 + + + or – + – or 0
TSH 0 + + or 0 + or 0 ? 0

“+” – increase; “++” – strong increase; “–” – decrease; 0 – no change; ? – unknow or unresolved.

general effect of exercise training is to attenuate the
NES responses: the hormonal concentrations during
exercise deviate less from resting homeostatic levels
in physically trained versus untrained people (37).
Thus, basically with more exercise training, an adapta-
tion goes on and exercise almost becomes more of
the “normal-like” state and less of a “stress-like” state
(19, 35). This adaptation not only results in typically
a smaller response in hormonal changes with exercise,
but in many examples, resting basal hormonal levels
are lower following exercise training. All of this is
thought to come about due to improved regulatory
capacity, increased receptor number in the target tis-
sue, and improved receptor sensitivity (2, 20). Much
further research work, however, is necessary in this
aspect of exercise endocrinology dealing with the
adaptation to exercise training. Such research work
will allow investigators to more clearly elucidate
exactly what is occurring not only within many of the
endocrine regulatory axes, but also in response to dif-
ferent types of specific exercise training.
There are exceptions to this adaptation phenome-
non. People who perform increasing amounts of exer-
cise training may ultimately subject themselves to
excessive quantities of high intensity exercise or grea-
ter and greater volumes of exercise in an attempt to
push themselves to do athletic-competitive levels of
exercise training. When they do this type of “hard,
disproportionate” training, the NES can be subjected
to tremendous levels of stress and respond accordingly
(in some cases greater than what had been observed
prior to conducting a training program) (2, 35, 39).
While there most certainly is an amazing adaptation
and plasticity capacity within the NES to deal with
exercise training, every system has its limits and can
slip into inappropriate responses if pushed too far (30,
40, 41). There are numerous research examples of
NES dysfunction and dysregulation developing in
persons involved with demanding or excessive exer-
cise training; such conditions as athletic amenorrhea,
the overtraining syndrome, exercise-hypothyroidism,
exercise osteopenia, and exercise-male hypogonadism
have all been reported (and attributed or linked to NES
abnormalities). There are excellent review articles
dealing with each of these topics in the research lite-
rature, and the reader is directed to these works if they
desire more information on the topic (see references
20, 25, 30, 41, 42).

Medicina (Kaunas) 2006; 42(10)

796 Anthony C. Hackney

Conclusion involves feed-forward and feedback regulatory loops.

In conclusion, an attempt was made to present a
brief, concise overview of the effects of exercise upon
the hormonal components that make up the neuro-
endocrine system. Specifically, four major topics, in
the form of questions, were addressed:
1) Is exercise a stressor to the neuroendocrine
system?
– The answer is yes, regardless of the mode of
exercise chosen. However, the degree of stress it
creates is influenced greatly by the intensity and
duration of the exercise, although there are many
factors that can modify that level of stress.
2) Why would exercise be a stressor to the neu-
roendocrine system?
– Exercise needs to be a stressor to the neuroen-
docrine system, so that the body can make the phy-
siological adaptations to be able to respond to the
exercise.
3) What are the effects of exercise as a stressor
upon the neuroendocrine system?
– The effects are profound and large, involving the
sympathetic nervous system and a variety of hypotha-
lamic-pituitary-peripheral gland axes. It shows a pro-
gression of phases in its responses and involves neural,
humoral, and hormonal stimuli as regulators and
4) Is exercise always a stress to the neuroendocrine
system?
– The answer is yes, although there is most cer-
tainly an adaptation response to that stress, such that
the stress becomes lessened with chronic exposure to
exercise training. However, even this system has limits
in its ability to adapt.
The answers to these questions are by no means
exhaustive or to be considered entirely complete and
definitive in nature. However, it is hoped the informa-
tion provided could serve as a beginning point for
those individuals interested in the fascinating aspects
of exercise physiology that deals with the neuroen-
docrine system.
Acknowledgement
The author wishes to thank his family, Grace, Sarah
and Zachary for their help in completing this work
and who are a source of immense pride, pleasure, and
motivation to him. This work is dedicated to my good
friend, colleague and mentor, Professor Dr. Atko Viru
of Tartu University, Estonia. At the time of develop-
ment for this article, the author was a Fulbright Scholar
in the Department of Physiology and Biochemistry
of the LKKA in Kaunas, Lithuania.

Fizinis krūvis kaip žmogaus neuroendokrininės sistemos stresą sukeliantis veiksnys

Anthony C. Hackney
Šiaurės Karolinos universiteto Fizinio lavinimo ir sporto mokslo katedros
Taikomosios fiziologijos laboratorijos Endokrinologijos skyrius,
Visuomenės sveikatos ir medicinos fakulteto Mitybos katedra, Chapel Hill, Šiaurės Karolina, JAV

Raktažodžiai: hormonai, fizinis aktyvumas, stresas.

Santrauka. Tai trumpa apžvalga apie fizinio krūvio sukelto streso poveikį pagrindinėms žmogaus
neuroendokrininės sistemos sudedamosioms dalims. Apžvalga suskirstyta į keturias temas, kurios pateiktos
bei pagrinėjamos klausimų forma. Šie klausimai yra: 1) ar fizinis krūvis yra stresą sukeliantis veiksnys
neuroendokrininei sistemai? 2) kodėl fizinis krūvis galėtų būti stresą sukeliančiu veiksniu neuroendokrininei
sistemai? 3) koks yra fizinio krūvio kaip stresą sukeliančio veiksnio poveikis neuroendokrininei sistemai? 4)
ar visada fizinis krūvis yra stresą sukeliantis veiksnys neuroendokrininei sistemai? Straipsnyje šie klausimai
pateikiami ir į juos atsakoma siekiant suteikti esminių žinių apie neuroendokrininį atsaką į fizinį krūvį.

Adresas susirašinėti: Professor Dr. A. C. Hackney, Applied Physiology Laboratory, University of North Carolina,
CB # 8700 Fetzer Building, Chapel Hill, NC 27599-8700, USA. El. paštas: ach@email.unc.edu

References
1. McArdle WD, Katch FI, Katch VL. Exercise physiology:
energy, nutrition, and human performance. Philadelphia (PA):
Williams and Wilkins; 1996.
2. Galbo H. Hormonal and metabolic adaptation to exercise.
Stuttgart (Germany): Georg Thieme Verlag; 1983.
3. Galbo H. The hormonal response to exercise. Diabetes Metab
Review 1986;1(4):385-408.
4. Viru A. The mechanism of training effects: a hypothesis. Int J

Medicina (Kaunas) 2006; 42(10)

 Exercise as a stressor to the human neuroendocrine system
Sports Med 1984;5(5):219-27.
5. Merriam-Webster Dictionary. 2004. Available from: URL:
http://www.m-w.com/.
6. National Library of Medicine, National Institutes of Health,
Washington DC. 2004. Available from: URL: http://www.
nlm.nih.gov/.
7. Rhoades R, Pflanzer R. Human physiology. 3rd ed. Fort Worth
(TX): Saunders College Publishing; 1996.
8. Rhoades RA, Tanner GA. Medical physiology. Boston (MA):
Little, Brown and Company; 1995.
9. Viru A, Viru M. Biochemical monitoring of sport training.
Champaign (IL): Human Kinetics Publishing; 2001.
10. Fahrner CL, Hackney AC. Effects of exercise on the binding
affinity of sex-hormone binding globulin for testosterone. Int
J Sports Med 1998;19(1):12-5.
11. Dill DB, Costill DL. Calculation and percentages in volumes
of blood, plasma, and red cells in dehydration. J Appl Physiol
1974;37:247-48.
12. McMurray RG, Hackney AC. Endocrine responses to exercise
and training. In: Garrett WE, Kirkendall DT, editors. Exercise
and Sport Science. Philadelphia (PA): Lippincott Williams &
Wilkins; 2000. p. 135-56.
13. Davies CTM, Few JD. Effects of exercise on adrenocortical
function. J Appl Physiol 1973;5:887-91.
14. Pollock ML, Wilmore JH. Exercise in health and disease. 2nd
ed. New York (NY): WB Saunders Co; 1990.
15. Galbo H, Hummer L, Peterson IB, Christensen NJ, Bie N.
Thyroid and testicular hormonal responses to graded and pro-
longed exercise in men. Eur J Appl Physiol 1977;36:101-6.
16. Fry AC, Kraemer WJ. Resistance exercise overtraining and
overreaching: neuroendocrine responses. Sports Med 1997;
23(2):106-29.
17. Kraemer WJ. Endocrine response to resistance exercise. Med
Sci Sports Exerc 1988;20:S152-7.
18. Kraemer WJ, Fleck SJ, Evans WJ. Strength and power
training: physiological mechanisms of adaptation. Exerc Sport
Sci Review 1996;24:363-97.
19. Galbo H. Influence of aging and exercise on endocrine func-
tion. Int J Sports Nutr Exerc Metab 2001;11:S49-57.
20. Hackney AC, Dobridge J. Exercise and male hypogonadism:
testosterone, the hypothalamic-pituitary-testicular axis, and
physical exercise In: Winters S, editor. Male hypogonadism:
basic, clinical, and therapeutic principles. Totowa: Humana
Press; 2003. p. 305-30.
21. Burger AG. Environment and thyroid function. J Clin Endo-
crinol Metab 2004;89(4):1526-28.
22. Viru A. Plasma hormones and physical exercise. Int J Sports
Med 1992;13:201-9.
23. Levy A. Physiological implications of pituitary trophic activity.
J Endocrinol 2002;174(2):147-55.
24. Viru A. Molecular cellular mechanisms of training effects. J
Sports Med Phys Fit 1994;34(4):309-22.
25. Loucks AB. Exercise training in the normal female: effects of
exercise stress and energy availability on metabolic hormones
Received 22 November 2005, accepted 17 August 2006
Straipsnis gautas 2005 11 22, priimtas 2006 08 17
Medicina (Kaunas) 2006; 42(10)
797
and LH pulsatility. In: Warren MP, Constantini NW, editors.
Sports endocrinology. Totowa: Humana Press; 2000. p. 165-
80.
26. Hackney AC, Premo MC, McMurray RG. Influence of aerobic
versus anaerobic exercise on the relationship between repro-
ductive hormones in men. J Sports Sci 1995;3:305-11.
27. Hackney AC, Viru A. Twenty-four cortisol response to mul-
tiple daily exercise sessions of moderate and high intensity.
Clin Physiol 1999;19:178-82.
28. Hackney AC, Sharp RL, Runyan WS, Ness RJ. Relationship
of resting prolactin and testosterone in males during intensive
training. Br J Sports Med 1989;23:194.
29. Kjaer M, Secher NH, Galbo H. Physical stress and catechola-
mine release. Baillieres Clin Endocrinol Metab 1987;1(2):279-
98.
30. Lehmann MJ, Lormes W, Opitz-Gress A, Steinacker JM,
Netzer N, Foster C, et al. Training and overtraining: an over-
view and experimental results in endurance sports. J Sports
Med Phys Fit 1997;37(1):7-17.
31. Widmaier EP. Metabolic feedback in mammalian endocrine
systems. Horm Metabc Res 1992;24:147-53.
32. Lacquemant C, Vasseur F, Leprete F, and Froguel P. Adipo-
cytokines, obesity and development of type 2 diabetes. Med
Sci (Paris) 2003;19(8-9):809-17.
33. Tsuchida K. Activins, myostatin and related TGF-beta family
members as novel therapeutic targets for endocrine, metabolic
and immune disorders. Curr Drug Targets: Imm Endocrine
Metab Disorders 2004;4(2):157-66.
34. Opstad PK. Androgenic hormones during prolonged physical
stress, sleep, and energy deficiency. J Clin Endocrinol Metab
1992;74(5):1176-83.
35. Viru A. Hormonal ensemble in exercise: hormones in muscular
activity. Volume 1. Boca Raton (FL): CRC Press; 1985.
36. Hackney AC, Fahrner CL, Stupnicki R. Reproductive hormo-
nal responses to maximal exercise in endurance-trained men
with low resting testosterone levels. Experimental and Clinical
Endocrinology: Diabetes 1997;105:291-5.
37. Hackney AC, Fahrner CL, Gulledge TP. Basal reproductive
hormonal profiles are altered in endurance trained men. J
Sports Med Phys Fit 1998;38:138-41.
38. McMurray RG, Eubank TK, Hackney AC. Nocturnal hor-
monal responses to resistance exercise. Eur J Appl Physiol
1995:72(1-2):121-26.
39. Kuopposalmi K, Naveri H, Harkonen N, Adlerkreutz H.
Plasma cortisol, androstenedione, testosterone and luteinizing
hormone in running exercise of various intensities. Scand J
Clin Lab Invest 1980;40:403-9.
40. Lehmann M, Foster C, Keul J. Overtraining in endurance ath-
letes: a brief review. Med Sci Sports Exerc 1993;25:854-62.
41. Urhausen A, Gabriel H, Kindermann W. Blood hormones as
markers of training stress and overtraining. Sports Med 1995;
20(4):251-76.
42. Arce JC, DeSouza MJ. Exercise and male factor infertility.
Sports Med 1993;5:146-69.